Continuous positioning apparatus and methods

ABSTRACT

Improved apparatus and methods for non-invasively assessing one or more parameters associated with systems such as fluidic circulating systems (e.g., the circulatory system of a living organism). In a first aspect, an improved method of continuously measuring pressure from a compressible vessel is disclosed, wherein a substantially optimal level of compression for the vessel is achieved and maintained using dynamically applied dither perturbations (e.g., modulation) on the various axes associated with the vessel. In a second aspect, an improved apparatus and method are provided for monitoring hemodynamic parameters, such as blood pressure, in a continuous and non-invasive manner while operating under a single unifying scheme. One variant of this scheme using a simulated annealing (SA) type approach to determining and maintaining an optimal operating state.

PRIORITY

This application is a continuation of and claims priority to co-ownedand co-pending U.S. patent application Ser. No. 13/965,058 of the sametitle, filed on Aug. 12, 2013, and issuing as U.S. Pat. No. 9,107,588 onAug. 18, 2015, which is a continuation of and claims priority to U.S.patent application Ser. No. 11/803,559 of the same title filed May 14,2007, issued as U.S. Pat. No. 8,506,497 on Aug. 13, 2013, which claimspriority to U.S. Provisional Patent Application Ser. No. 60/800,164filed May 13, 2006 of the same title, each of the foregoing beingincorporated herein by reference in its entirety.

COPYRIGHT

A portion of the disclosure of this patent document contains materialthat is subject to copyright protection. The copyright owner has noobjection to the facsimile reproduction by anyone of the patent documentor the patent disclosure, as it appears in the Patent and TrademarkOffice patent files or records, but otherwise reserves all copyrightrights whatsoever.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates generally to methods and apparatus for monitoringparameters associated with fluid systems, and specifically in one aspectto the non-invasive monitoring of arterial blood pressure in a livingsubject.

2. Description of Related Technology

The accurate, continuous, non-invasive measurement of blood pressure haslong been sought by medical science. The availability of suchmeasurement techniques would allow the caregiver to continuously monitora subject's blood pressure accurately and in repeatable fashion withoutthe use of invasive arterial catheters (commonly known as “A-lines”) inany number of settings including, for example, surgical operating roomswhere continuous, accurate indications of true blood pressure are oftenessential.

Several well known techniques have heretofore been used tonon-invasively monitor a subject's arterial blood pressure waveform,namely, auscultation, oscillometry, and tonometry. Both the auscultationand oscillometry techniques use a standard inflatable arm cuff thatoccludes the subject's peripheral (predominately brachial) artery. Theauscultatory technique determines the subject's systolic and diastolicpressures by monitoring certain Korotkoff sounds that occur as the cuffis slowly deflated. The oscillometric technique, on the other hand,determines these pressures, as well as the subject's mean pressure, bymeasuring actual pressure changes that occur in the cuff as the cuff isdeflated. Both techniques determine pressure values only intermittently,because of the need to alternately inflate and deflate the cuff, andthey cannot replicate the subject's actual blood pressure waveform.Thus, continuous, beat-to-beat blood pressure monitoring cannot beachieved using these techniques.

Occlusive cuff instruments of the kind described briefly above havegenerally been somewhat effective in sensing long-term trends in asubject's blood pressure. However, such instruments generally have beenineffective in sensing short-term blood pressure variations, which areof critical importance in many medical applications, including surgery.

The technique of arterial tonometry is also well known in the medicalarts. According to the theory of arterial tonometry, the pressure in asuperficial artery with sufficient bony support, such as the radialartery, may be accurately recorded during an applanation sweep when thetransmural pressure equals zero. The term “applanation” refers to theprocess of varying the pressure applied to the artery. An applanationsweep refers to a time period during which pressure over the artery isvaried from over-compression to under-compression or vice versa. At theonset of a decreasing applanation sweep, the artery is over-compressedinto a “dog bone” shape, so that pressure pulses are not recorded. Atthe end of the sweep, the artery is under-compressed, so that minimumamplitude pressure pulses are recorded. Within the sweep, it is assumedthat an applanation occurs during which the arterial wall tension isparallel to the tonometer surface. Here, the arterial pressure isperpendicular to the surface and is the only stress detected by thetonometer sensor. At this pressure, it is assumed that the maximumpeak-to-peak amplitude (the “maximum pulsatile”) pressure obtainedcorresponds to zero transmural pressure. Note that other measuresanalogous to maximum pulsatile pressure, including maximum rate ofchange in pressure (i.e., maximum dP/dT) can also be implemented.

One prior art device for implementing the tonometry technique includes arigid array of miniature pressure transducers that is applied againstthe tissue overlying a peripheral artery, e.g., the radial artery. Thetransducers each directly sense the mechanical forces in the underlyingsubject tissue, and each is sized to cover only a fraction of theunderlying artery. The array is urged against the tissue to applanatethe underlying artery and thereby cause beat-to-beat pressure variationswithin the artery to be coupled through the tissue to at least some ofthe transducers. An array of different transducers is used to ensurethat at least one transducer is always over the artery, regardless ofarray position on the subject. This type of tonometer, however, issubject to several drawbacks. First, the array of discrete transducersgenerally is not anatomically compatible with the continuous contours ofthe subject's tissue overlying the artery being sensed. This can resultin inaccuracies in the resulting transducer signals. In addition, insome cases, this incompatibility can cause tissue injury and nervedamage and can restrict blood flow to distal tissue.

Other prior art techniques have sought to more accurately place a singletonometric sensor laterally above the artery, thereby more completelycoupling the sensor to the pressure variations within the artery.However, such systems may place the sensor at a location where it isgeometrically “centered” but not optimally positioned for signalcoupling, and further typically require comparatively frequentre-calibration or repositioning due to movement of the subject duringmeasurement.

Tonometry systems are also commonly quite sensitive to the orientationof the pressure transducer on the subject being monitored. Specifically,such systems show degradation in accuracy when the angular relationshipbetween the transducer and the artery is varied from an “optimal”incidence angle. This is an important consideration, since no twomeasurements are likely to have the device placed or maintained atprecisely the same angle with respect to the artery. Many of theforegoing approaches similarly suffer from not being able to maintain aconstant angular relationship with the artery regardless of lateralposition, due in many cases to positioning mechanisms which are notadapted to account for the anatomic features of the subject, such ascurvature of the wrist surface.

Furthermore, compliance in various apparatus components (e.g., the strapand actuator assembly) and the lack of soft padding surrounding thesensor which minimizes edge effects may adversely impact the accuracy oftonometric systems to a significant extent.

One very significant limitation of prior art tonometry approachesrelates to the magnitude and location of the applied applanationpressure during varying conditions of patient motion, position, meanpressure changes, respiration, etc. Specifically, even when the optimumlevel of arterial compression at the optimal coupling location isinitially achieved, there is commonly real-world or clinical factorsbeyond reasonable control that can introduce significant error into themeasurement process, especially over extended periods of time. Forexample, the subject being monitored may voluntarily or involuntarilymove, thereby altering (for at least a period of time) the physicalrelationship between the tonometric sensor and the subject'stissue/blood vessel. Similarly, bumping or jarring of the subject or thetonometric measurement apparatus can easily occur, thereby againaltering the physical relationship between the sensor and subject. Thesimple effect of gravity can, under certain circumstances, cause therelative positions of the sensor and subject blood vessel to alter withtime as well.

Furthermore, physiologic responses of the subject (including, forexample, relaxation of the walls of the blood vessel due to anesthesiaor pharmacological agents) can produce the need for changes in theapplanation level (and sometimes even the lateral/proximal position ofthe sensor) in order to maintain optimal sensor coupling. Additionally,due to the compliance of surrounding tissue and possibly measurementsystem, the applanation level often needs to adjust with changes in meanarterial pressure.

Several approaches have heretofore been disclosed in attempts to addressthe foregoing limitations. In one prior art approach, an occlusive cuffis used to provide a basis for periodic calibration; if the measuredpressure changes a “significant” amount or a determined time haselapsed, then the system performs a cuff calibration to assist inresetting the applanation position. Reliable pressure data is notdisplayed or otherwise available during these calibration periods. Seefor example U.S. Pat. No. 5,261,414 to Aung, et al issued Nov. 16, 1993and entitled “Blood-Pressure Monitor Apparatus,” assigned to ColinCorporation (hereinafter “Aung”). See also U.S. Pat. No. 6,322,516issued Nov. 27, 2001 and entitled “Blood-Pressure Monitor Apparatus,”also assigned to Colin Corporation, wherein an occlusive cuff is used asthe basis for calibration of a plurality of light sensors.

In another prior art approach, a pressure cuff or a pelotte equippedwith a plethysmographic gauge, such as an impedance or a photo-electricdevice, is used to drive a servo control loop. See, e.g., U.S. Pat. No.4,869,261 to Penaz issued Sep. 26, 1989 and entitled “Automaticnoninvasive blood pressure monitor,” assigned to University J.E. Purkynev Brne (hereinafter “Penaz”). In this device, the sensor is connectedthrough at least one amplifier and a phase corrector to anelectro-pressure transducer. All these components constitute the closedloop of a servo control system which (at least ostensibly) continuouslychanges the pressure in the cuff and attempts to maintain the volume ofthe artery at a value corresponding to zero tension across the arterialwall. The servo control system loop further includes a pressurevibration generator, the frequency of vibration being higher than thatof the highest harmonic component of blood pressure wave. A correctioncircuit is also provided, the input of which is connected to theplethysmographic sensor and output of which is provided to correct thesetpoint of the servo control system. The Penaz system therefore ineffect constantly “servos” (within a cardiac cycle) to a fixed lightsignal level received from the sensor. Unlike the Colin systemsdescribed above, the system continuously displays pressure to theoperator. However, the operation of the plethysmographic sensor of Penazlimited the application of this device to a peripheral section of a limb(preferably a finger) where the peripheral pressure, especially underconditions of compromised peripheral circulation, may not accuratelyreflect aortic or brachial artery pressure. This presents a potentiallysignificant cause of error.

Yet another prior art approach uses a series of varying pressure“sweeps” performed successively to attempt to identify the actualintra-arterial blood pressure. The applanation pressure applied duringeach of these sweeps is generally varied from a level of arterialunder-compression to over-compression (or vice-versa), and the systemanalyzes the data obtained during each sweep to identify, e.g., thelargest pressure waveform amplitude. See, e.g., U.S. Pat. No. 5,797,850to Archibald, et al issued Aug. 25, 1998 and entitled “Method andapparatus for calculating blood pressure of an artery,” assigned toMedwave, Inc. (hereinafter “Archibald”). The system of Archibald is nottruly continuous, however, since the sweeps each require a finite periodof time to complete and analyze. In practice the sweeps are repeatedwith minimal delay, one after another, throughout the operation of thedevice. During applanation mechanism resetting and subsequent sweepoperations, the system is effectively “dead” to new data as it analyzesand displays the data obtained during a previous sweep period. This isclearly disadvantageous from the standpoint that significant portions ofdata are effectively lost, and the operator receives what amounts toonly periodic indications of the subject's blood pressure (i.e., one newpressure beat display every 15-40 seconds).

Lastly, the techniques for non-invasive pressure measurement disclosedby the Assignee of the present invention in U.S. Pat. Nos. 6,228,034,6,176,831, 5,964,711, and 5,848,970, each entitled “Apparatus and methodfor non-invasively monitoring a subject's arterial blood pressure” andincorporated herein by reference in their entirety, include modulationof applanation level at, inter alia, frequencies higher than the heartrate (e.g., sinusoidal perturbation at 25 Hz). Further, Assignee hasdetermined over time that it is desirable in certain circumstances tocontrol the applanation level according to other modulation schemesand/or frequencies, and/or which are not regular or deterministic innature, such as those disclosed by co-owned U.S. Pat. No. 6,974,419,entitled “Method and apparatus for control of non-invasive parametermeasurements” and incorporated herein by reference in its entirety. Eachof the foregoing methods, however, distinguishes between two modes ofoperation, the first being (1) calibration; and the second being knownas (2) patient monitoring mode (“PMM”).

“Simulated Annealing”

Simulated annealing (SA) is a term that relates to optimization schemathat are related to or modeled generally after physical processes. Forexample, one branch of simulated annealing theory is a generalization ofa Monte Carlo method for examining the equations of state and frozenstates of n-body systems. The concept is based to some degree on themanner in which liquids freeze or metals recrystalize during thephysical process of annealing. In an annealing process, materialinitially at high temperature and disordered, is cooled so as toapproximately maintain thermodynamic equilibrium. As cooling proceeds,the system becomes more ordered and approaches a “frozen” ground stateat Temperature (T)=0. Accordingly, SA can be thought of as analogous toan adiabatic approach to the lowest energy state. If the startingtemperature of the system is too low, or the cooling regimen isinsufficiently slow, the system may form defects or freeze inmeta-stable states; i.e., become trapped in a local minimum energystate.

One scheme (Metropolis) selects an initial state of a thermodynamicsystem (energy E and temperature T), and holding T constant, the initialconfiguration is perturbed, and the change in energy (dE) determined. Ifthe change in energy is negative, the new configuration is accepted. Ifthe change in energy is positive, it is accepted with a probabilitydetermined by the Boltzmann factor exp−(dE/T). This processes is thenrepeated sufficient times to give adequate sampling statistics for thecurrent temperature. The temperature is then decremented, and the entireprocess repeated until a “frozen” state is achieved (at T=0).

This Monte Carlo approach can be analogized to combinatorial problems.The current state of the thermodynamic system is analogous to thecurrent solution to the problem. The energy equation for thethermodynamic system is analogous to the objective function. The groundstate is analogous to the global minimum.

A significant difficulty in implementing this algorithm, however, isthat there is often no obvious analogy for the temperature (T) withrespect to a parameter in the combinatorial problem. Furthermore,avoidance of entrainment in local minima (quenching) is dependent on an“annealing schedule”, the choice of initial temperature, the number ofiterations performed at each temperature, and how much the temperatureis decremented at each step as cooling proceeds.

Based on the foregoing, there is needed an improved apparatus andmethodology for accurately and continuously controlling the non-invasivemeasurement of parameters such as pressure. Such improved methodologyand apparatus would ideally integrate the highly efficient simulatedannealing (SA) approach and allow for, inter alia, continuousmeasurement (tonometrically or otherwise) of one or more physiologic orhemodynamic parameters, the measured values of such parameters beingreflective of true (e.g., intra-arterial) parameters, while alsoproviding robustness and repeatability under varying environmentalconditions including motion artifact and other noise. In addition, suchmethod and apparatus would operate under a substantially unified scheme,as opposed to the two or more independent schemes modeled in prior artdevices.

Such a method and apparatus would also be easily utilized by trainedmedical personnel and untrained individuals, thereby allowing subjectsto accurately and reliably conduct self-monitoring if desired.

SUMMARY OF THE INVENTION

In a first aspect of the invention, transient-resistant apparatus fordetermining the blood pressure of a living subject is disclosed. In oneembodiment, this comprises a processor and a computer program running onsaid processor, said program comprising at least one simulated annealingrelated algorithm.

In a second aspect of the invention, a method of determining hemodynamicparameters using a simulated annealing-based algorithm is disclosed.

In a third aspect of the invention, a computer storage medium comprisinga computer program adapted for substantially unified mode operationaccording to a simulated annealing algorithm is disclosed.

In a fourth aspect of the invention, a method of maintaining asubstantially optimal level of compression for the vessel usingdynamically applied dither perturbations on at least one axes associatedwith the vessel is disclosed.

In a fifth aspect of the invention, a method of treating a livingsubject based on simulated annealing techniques for assessinghemodynamic parameter(s) is disclosed.

In a sixth aspect of the invention, a method of compensating fortransient events so as to maintain a hemodynamic assessment process in asubstantially optimal state is disclosed.

In a seventh aspect, a method of maintaining an optimal level ofcompression between one or more sensors and a vessel is disclosed. Inone embodiment, the method includes: (i) disposing the one or moresensors at a first location of the vessel; (ii) determining whether aplurality of signals from the one or more sensors are detected; (iii)based on the determination, generating a first dither sequence; (iv)relocating the one or more sensors to a second location in accordancewith the first dither sequence; and (v) receiving a plurality ofmeasurements from the one or more sensors at the second location.

In an eighth aspect, a transient-resistant apparatus configured tomaintain an optimal level of compression between one or more sensors anda vessel is disclosed. In one embodiment, the apparatus includes: theone or more sensors configured to be disposed proximate the vessel; anda digital processor configured to run a computer program thereon, thecomputer program comprising a plurality of instructions which areconfigured to, when executed: (i) analyze a plurality of signalsgenerated by the one or more sensors; (ii) generate a plurality ofcontrol signals for a motor configured to adjust a position of the oneor more sensors; (iii) obtain first data about one or more firstparameters measured by the one or more sensors at a first location onthe vessel; and (iv) store the first data.

In a ninth aspect, a computer readable apparatus is disclosed. In oneembodiment, the apparatus includes a computer program having a pluralityof instructions, for the program adapted for a substantially unifiedmode operation and configured to execute a simulated annealingalgorithm, the algorithm being useful for maintaining an optimal levelof compression between one or more sensors and a vessel therefrom. Inone variant, the plurality of instructions are configured to, whenexecuted: (i) receive a first plurality of signals from one or moresensors; (ii) process the first plurality of signals in order todetermine an optimized location of the one or more sensors; (iii)instruct the one or more sensors to relocate to the optimized location;and (iv) determine the one or more parameters at the optimized location.

These and other features of the invention will become apparent from thefollowing description of the invention, taken in conjunction with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flow diagram illustrating the fundamental process stepsperformed in accordance with one exemplary embodiment of the controlmethodology of the present invention.

FIG. 2 is a flow diagram illustrating the operation of the exemplaryembodiment of the first (annealing entry) process of FIG. 1.

FIG. 2a is a graph illustrating starting system temperature as afunction of initial pulse pressure for one exemplary embodiment of thepresent invention.

FIG. 3 is a flow diagram illustrating the operation of one exemplaryembodiment of the second process (dither generation) of FIG. 1.

FIG. 3a is a flow diagram illustrating one exemplary process flow fordetermining the next dither pair sequence and executing the dither pairof FIG. 3.

FIG. 3b is a flow diagram illustrating one exemplary process flow forgenerating, transforming and baking a unit dither according to oneembodiment of the present invention.

FIG. 3c is a flow diagram illustrating one exemplary process flow forcollecting beat data in accordance with one embodiment of the presentinvention.

FIG. 3d is a graph illustrating the drawbacks of fixed applanationdither size as it applies to slew-rate limiting in accordance with theprinciples of the present invention.

FIG. 3e is a graph illustrating the probability of an applanation-onlydither as a function of temperature in accordance with one embodiment ofthe present invention.

FIG. 3f is a graph illustrating the temperature coefficient as afunction of temperature in accordance with one embodiment of the presentinvention.

FIG. 3g is a graph illustrating temperature as a function of number ofbeats to collect in accordance with one embodiment of the presentinvention.

FIG. 4 is a flow diagram illustrating the operation of one exemplaryembodiment of the third process (e.g. hemodynamic parameter processing)according to the invention.

FIG. 4a is a graph illustrating PMM bias as a function of mean pressurein accordance with one embodiment of the present invention.

FIG. 4b is a graph illustrating PMM bias temperature factor as afunction of temperature in accordance with one embodiment of the presentinvention.

FIG. 4c is a graph illustrating delta energy as a function of deltapulse pressure in accordance with the principles of the presentinvention.

FIG. 4d is a graph illustrating transition probabilities as a functionof pulse pressure and temperature in accordance with one embodiment ofthe present invention.

FIG. 5 is a flow diagram illustrating the operation of one exemplaryembodiment of the fourth process (e.g. adapting behavior of system) ofFIG. 1.

FIG. 5a is a graph illustrating average mean as a function oftemperature tax in accordance with one embodiment of the presentinvention.

FIG. 6 is a block diagram of one exemplary embodiment of the apparatusfor hemodynamic parameter assessment within the blood vessel of a livingsubject according to the invention.

DETAILED DESCRIPTION OF THE INVENTION

Reference is now made to the drawings wherein like numerals refer tolike parts throughout.

It is noted that while the invention is described herein primarily interms of a apparatus and methods for the control of non-invasivemeasurements of hemodynamic parameters such as blood pressure obtainedvia the radial artery (i.e., wrist) of a human subject, the inventionmay also be readily embodied or adapted to monitor such parameters atother blood vessels and locations on the human body, as well asmonitoring these parameters on other warm-blooded species. Similarly,the techniques of the present invention can be applied to otherparameters, as well as other similar fluidic systems which have similarproperties to those of the circulatory system of a living being. Allsuch adaptations and alternate embodiments are readily implemented bythose of ordinary skill in the relevant arts, and are considered to fallwithin the scope of the claims appended hereto.

As used herein, the term “continuous” is meant to include withoutlimitation continuous, piece-wise continuous, and/or substantiallycontinuous processes (e.g., those which are generally continuous innature, but are not per se continuous).

As used herein, the term “hemodynamic parameter” is meant to includeparameters associated with the circulatory system of the subject,including for example pressure (e.g., diastolic, systolic, pulse, ormean pressure), derivatives or combinations thereof, arterial flow,arterial wall diameter (and its derivatives), cross sectional area ofthe artery, and arterial compliance.

Additionally, it is noted that the terms “tonometric,” “tonometer,” and“tonometry” as used herein are intended to broadly refer to non-invasivesurface measurement of one or more hemodynamic parameters, such as byplacing a sensor in communication with the surface of the skin, althoughcontact with the skin need not be direct, and can be indirect (e.g.,such as through a coupling medium or other interface).

The terms “applanate” and “applanation” as used herein refer to, withoutlimitation, the compression (relative to a state of non-compression) oftissue, blood vessel(s), and other structures such as tendon or muscleof the subject's physiology. Similarly, an applanation “sweep” refers toone or more periods of time during which the applanation level is varied(either increasingly, decreasingly, or any combination thereof).Although generally used in the context of linear (constant velocity)position variations, the term “applanation” as used herein mayconceivably take on any variety of other forms, including withoutlimitation (i) a continuous non-linear (e.g., logarithmic) increasing ordecreasing compression over time; (ii) a non-continuous or piece-wisecontinuous linear or non-linear compression; (iii) alternatingcompression and relaxation; (iv) sinusoidal or triangular wavesfunctions; (v) random motion (such as a “random walk”; or (vi) adeterministic profile. All such forms are considered to be encompassedby these terms.

As used herein, the term “epoch” refers to any increment of time,ranging in duration from the smallest measurable fraction of a second tomore than one second.

As used herein, the terms “spatial” and “position”, although describedin terms of a substantially Cartesian coordinate system havingapplanation (i.e., Z-axis), lateral (X-axis) and (Proximal refers tocloser to the heart) longitudinal or (proximal—distal) (Y-axis)components, shall refer to any spatial coordinate system including,without limitation, cylindrical, spherical, and polar. Such use ofalternate coordinate systems may clearly be independent of anyparticular hardware configuration or geometry (e.g., by performingsimple mathematical translations between a Cartesian-based apparatus andthe non-Cartesian coordinate system), or alternatively make advantageoususe of such geometries. The present invention is therefore in no waylimited to certain coordinate systems of apparatus configurations. Asone example, it will be recognized that the methods and apparatus of thepresent invention may be embodied using a cylindrical coordinate systemmodeled around the radial artery, such that a particular point in spacefor the tonometric sensor(s) can be specified by the Z, r, and θparameters. This approach may have advantages since the forearm/wristarea of the human being very roughly comprises a cylindrical form.

As used herein, the term “temperature” refers to, without limitation,any parameter which can be correlated or analogized to temperature in anactual or physical annealing process including, for example, confidencelevel. Temperature as used in the context of the SA models disclosedherein is merely an abstract concept representative of a quantity orproperty associated with the system being controlled or modeled.

As used herein, the term “application” (in the context of a softwareapplication) refers generally to a unit of executable software thatimplements a certain functionality or theme. The themes of applicationsvary broadly across any number of disciplines and functions (such ason-demand content management, e-commerce transactions, brokeragetransactions, home entertainment, calculator etc.), and one applicationmay have more than one theme. The unit of executable software generallyruns in a predetermined environment; for example, the unit couldcomprise a downloadable Java Xlet™ that runs within the JavaTV™environment.

As used herein, the term “computer program” or “software” is meant toinclude any sequence or human or machine cognizable steps which performa function. Such program may be rendered in virtually any programminglanguage or environment including, for example, C/C++, Fortran, COBOL,PASCAL, assembly language, markup languages (e.g., HTML, SGML, XML,VoXML), and the like, as well as object-oriented environments such asthe Common Object Request Broker Architecture (CORBA), Java™ (includingJ2ME, Java Beans, etc.) and the like.

As used herein, the term “integrated circuit (IC)” refers to any type ofdevice having any level of integration (including without limitationULSI, VLSI, and LSI) and irrespective of process or base materials(including, without limitation Si, SiGe, CMOS and GaAs). ICs mayinclude, for example, memory devices (e.g., DRAM, SRAM, DDRAM,EEPROM/Flash, ROM), digital processors, SoC devices, FPGAs, ASICs, ADCs,DACs, transceivers, memory controllers, and other devices, as well asany combinations thereof.

As used herein, the term “memory” includes any type of integratedcircuit or other storage device adapted for storing digital dataincluding, without limitation, ROM. PROM, EEPROM, DRAM, SDRAM, DDR/2SDRAM, EDO/FPMS, RLDRAM, SRAM, “flash” memory (e.g., NAND/NOR), andPSRAM.

As used herein, the terms processor, “microprocessor” and “digitalprocessor” are meant generally to include all types of digitalprocessing devices including, without limitation, digital signalprocessors (DSPs), reduced instruction set computers (RISC),general-purpose (CISC) processors, microprocessors, gate arrays (e.g.,FPGAs), PLDs, reconfigurable compute fabrics (RCFs), array processors,and application-specific integrated circuits (ASICs). Such digitalprocessors may be contained on a single unitary IC die, or distributedacross multiple components.

Overview

In one fundamental aspect, the present invention comprises apparatus andmethods for controlling an applanation or other positioning mechanismused in physiologic analysis such as, e.g., non-invasive hemodynamicparameter measurements in order to, inter alia, maintain optimalcoupling between a parameter sensor and the blood vessel of interest.These improved apparatus and methods are based on simulated annealing(SA) paradigms that provide a substantially unified and highly effectivemeans for placing and maintaining the hemodynamic assessment or othersuch system in an optimized operational state. Maintenance of this statecorrelates, inter alia, to the best possible accuracy for theparameter(s) (e.g., blood pressure) being measured.

Exemplary techniques for determining the optimal applanation level,position, and coupling that can be utilized with or benefit from thepresent invention are described in detail in, e.g., co-owned U.S. Pat.No. 6,730,038 entitled “Method And Apparatus For Non-InvasivelyMeasuring Hemodynamic Parameters Using Parametrics” issued May 4, 2004and co-owned U.S. Pat. No. 6,974,419 entitled “Method and Apparatus forControl of Non-Invasive Parameter Measurements” issued Dec. 13, 2005each of which are incorporated by reference herein in their entirety.

The improved techniques and apparatus of the present inventionadvantageously may be used with a broad range of hardwareconfigurations, including e.g., a single sensor (or array of sensors) asdescribed in detail herein and the aforementioned and incorporatedapplications, or in conjunction with literally any type of otherapparatus adapted for hemodynamic parameter measurement, including forexample the devices described in U.S. patent application Ser. No.09/815,982 entitled “Method and Apparatus for the Noninvasive Assessmentof Hemodynamic Parameters Including Blood Vessel Location” filed on Mar.22, 2001 and patented as U.S. Pat. No. 7,503,896 on Mar. 17, 2009, andU.S. patent application Ser. No. 09/815,080 entitled “Method andApparatus for Assessing Hemodynamic Parameters within the CirculatorySystem of a Living Subject” also filed on Mar. 22, 2001 and patented asU.S. Pat. No. 7,048,691 on May 23, 2006, both of which are assigned tothe assignee hereof and incorporated herein by reference in theirentirety. For example, an entirely tonometric pressure-based approachcan be used. Alternatively, ultrasound measurements of blood pressurevia blood flow kinetic energy or velocity can be used as a confirmatorytechnique for the tonometric pressure-based approach. As anotherexample, lateral positioning based on analysis of the acoustic signalsrelating to vessel wall detection may be used in addition to (or inplace of) the pressure-based techniques described in the cited co-ownedpatents and patent applications.

Hence, the various aspects of the present invention are advantageouslycompatible with a number of different physiologic and hemodynamicassessment techniques. It will also be recognized that the techniquesand apparatus described herein are in no way limited to tonometricapplications; rather, these features may be implemented even in e.g.,occlusive cuff or pellot-based systems.

While the techniques described in the aforementioned co-pending patentand patent applications have been determined by Assignee to be highlyeffective, their robustness and utility in practical (e.g., clinical)settings is enhanced through the addition of one or more of the variousaspects of the present invention. In the context of blood pressuremeasurement, existing approaches to acquire and measure the patient'smean arterial blood pressure focused on the compression of the patient'stissues at a location directly over their artery of interest (e.g., theradial artery) such that the observed pulse pressure was maximized. Itis at this point of maximum pulse pressure that the pressure exerted onthe compressed artery equals the mean arterial pressure. Observance ofthe mean arterial pressure in an accurate way was largely predicated onlocating the artery correctly, and compressing the artery at anappropriate level of applanation.

Under some such approaches, location of the artery was accomplishedusing two discrete steps or phases. First during an initial calibrationphase, a scan of a narrow portion of an acquisition space is performedby making broad movements along both the lateral and applanation axes.Second, during the second phase of operation, the applanation locationis fine tuned using a series of small experimental dithers around thecurrent operating point located during the calibration phase. In thisway, the two phases of artery location and applanation can be viewed asa “large signal experiment” followed by a “small signal experiment”.

While there normally is no sense that a large signal experiment isbetter or worse than a small signal experiment, there are some issuesintroduced to the system under measurement by implementing such anapproach. First, the observed pulse pressure may not only be a functionof the actual position of the transducer with respect to the artery, butit quite probably is also a function of the history of stresses placedupon the involved tissues by the actuator. It would therefore bereasonable to expect that this historical effect may be amplified withlarger disturbances of the system seen during initial calibration.

Second, using two separate modes of operation assumes that the system(i.e. the transducer, actuator and patient's tissues) will respondsimilarly during both large signal and small signal experiments, ineffect assuming the system behaves in a linear fashion. However, theoperating point located during the initial calibration phase and theoperating point located during the second phase may be two different“answers” that are only appropriate to their own respective phases ofoperation. In systems where only small adjustments are made to theapplanation position and the lateral position subsequent to calibration,such a two phase solution can be problematic as the operating pointlocated during calibration may not be the ideal operating point locationfor the second phase and the control system can have a tendency to getstuck at a local, as opposed to global, maxima.

Therefore in accordance with one embodiment of the invention, a methodand apparatus are provided for monitoring hemodynamic parameters, suchas blood pressure, in a continuous and non-invasive manner whileoperating under a single unifying scheme. In a sense, this approachacknowledges the fact that we are constantly calibrating, alwaysquestioning whether or not we are at the patient's optimal operatingpoint to measure the hemodynamic parameter of interest. One embodimentof the invention includes a measurement apparatus for measuring varioushemodynamic parameters associated with the human body. In addition, adigital processor is disclosed for calculating various parameters inresponse to the measured parameters. Additionally, the inventionincludes a method and apparatus for controlling the location of themeasurement in response to information generated by the digitalprocessor.

In accordance with a described embodiment of the hemodynamic systemmonitoring apparatus, the hemodynamic system apparatus implements a“simulated annealing” process which unifies measurements under a singlescheme of operation. In one exemplary embodiment of the simulatedannealing process, dithers of varying sizes will be dynamically appliedto the system around a given operating point. The size of these ditherswill be correlated to a confidence analysis (e.g. so-called temperaturemeasurement), such that larger changes to dither will be applied whenconfidence is low while smaller more subtle changes will be used whenconfidence is high. This simulated annealing process will be moreresilient against being trapped by so-called local maxima over prior arttechniques, as well as being more resilient against varying topologiesof hemodynamic parameter curves. This approach also opens up thesolution space to the maximum amount allowed by the physical actuatorimplemented (i.e. by allowing for adjustment in the applanation, lateraland distal axes either serially or in parallel) and by further allowingfor dynamic adjustment of the position of the transducer over the radialartery further improving the reliability and robustness of these classesof non-invasive hemodynamic parameter monitors. Further, because theunifying scheme is largely a “small signal” approach, although notnecessarily so due to factors such as the aforementioned optimalpositioning confidence level, disruptions to the system causinginaccurate non-invasive readings are effectively minimized.

Continuous Positioning Methodology

It will also be recognized that while the process of the presentinvention is described subsequently herein with respect to a tonometricpressure sensor or transducer, it can be applied more generally to othersignal domains including without limitation ultrasonics andelectromagnetic radiation (e.g., IR, X-ray, etc.).

Furthermore, it will be appreciated that while primarily described inthe context of the aforementioned tonometric apparatus (i.e., atonometric pressure sensor which also acts to provide varying levels ofcompression of the underlying tissue and blood vessel(s)), themethodology of the present invention may be practiced using apparatushaving separate components which provide these functions. For example,the control of the pressure sensor may be partly or completely decoupledfrom the applanation control system, such that the level of applanationcan be varied independently from the coupling of the active surface(s)of the sensor. A detailed discussion of exemplary electronic and signalprocessing apparatus used to support the operation of the processesdescribed herein is provided with respect to FIG. 6 below.

It will be recognized by those of ordinary skill that the logicalprocesses of the present invention may also be practiced entirelyalgorithmically (e.g., in software) and/or firmware.

FIG. 1 is a flow chart illustrating the general control methodologyperformed to determine, e.g., the hemodynamic parameter(s) (bloodpressure, etc.) of a living subject in accordance with one embodiment ofthe present invention. The overall process can be thought of asconstituting four (4) basic methodological steps. The first step 102comprises the step of entry into the “simulated annealing” process andthe pre-requisite calculations for the steps that follow. This firststep 102 is described further in detail with regards to FIG. 2 and itsaccompanying disclosure.

It will be appreciated that the term “simulated annealing” as usedherein is merely used as an analogy for sake of easier understanding ofthe concepts of the invention, and in no way carries any specificconnotation or meaning.

In step 104, the variation (e.g., dither) generation process isinitiated. The set of dither factors typically includes an applanationdither factor, a lateral dither factor and a distal dither factor,corresponding to the applanation, lateral and distal axes respectivelyfor the measuring apparatus. The dither generation process is discussedfurther herein with regards to FIG. 3 and its accompanying disclosure.Alternative embodiments of the invention described herein may includemore or less dither factors and/or axes of interest and implementationwould be readily apparent to one of ordinary skill given the presentdisclosure herein.

Step 106 corresponds to the pressure signal processing methodologyutilized with regards to the present embodiment of the invention. Thismethodology is described in further detail with and in part with regardsto FIG. 4 and its accompanying disclosure.

In step 108, the system behavior is adjusted based on the aforementioneddither generation and hemodynamic parameter processing steps. Generallyspeaking, as the confidence level of being located at the optimal pointdecreases the dither factors utilized are increased in order to allowfor “larger” searches of the optimal positioning point, this optimalpoint being the ideal location from which to obtain hemodynamicparameter readings. Conversely, as the confidence level increases, thedither factor is decreased in order to allow only “smaller” searches forthe optimal point in order to obtain hemodynamic parameter readings,while simultaneously minimizing adverse influences on the system as aresult of the non-invasive measurement. This adaptive behavior isdiscussed further with regards to FIG. 5 and its accompanyingdisclosure.

At this point, the process 100 may end or alternatively the process maycontinue by performing a new measurement at 102 and repeating one ormore of the aforementioned processes. For purposes of simplicity andbrevity, processes 102, 104, 106 and 108 will be primarily discussedwith regards to only two axes of interest (i.e., applanation andlateral), although it is recognized that more or less axes processingsteps could be implemented consistent with the principles of the presentinvention.

(1) Simulated Annealing Entry

Referring now to FIG. 2, one exemplary embodiment of the simulatedannealing entry process 102 is shown. While the exemplary simulatedannealing process is described in conjunction with the use of tonometricblood pressure monitoring system, such as for example the TL-150developed and marketed by Tensys® Medical, Inc., the invention is in noway so limited. In fact, the process discussed with regards to FIG. 2may be utilized within the framework of a plurality of differentapparatus measuring other physiologic or hemodynamic parameters, theaforementioned TL-150 merely being exemplary.

In step 202, a pressure transducer is applanated along the applanationaxis at a desired location; e.g., a palpation mark determined by a user,or location determined via vessel location mechanism or technique suchas ultrasound or the like. In a first embodiment, the palpation mark isdetermined manually by first, palpating the radial styloid process andthen drawing a transverse line over this bone. Next, the location of thepatient's pulse is determined and the user will draw a lineperpendicular to and intersecting the transverse line previously drawn.The intersection of this line will be referred to herein as thepalpation mark. While discussed in terms of locating along the radialstyloid process on a patient's wrist, the palpation technique describedherein could be equally applicable to other areas of the human body,such as e.g. the ulnar pulse point, carotid pulse point, or brachialpulse point, etc. The measuring apparatus is then placed over thepalpation mark and the pressure transducer will applanate the patient'stissue at the palpation mark to a specified applanation pressure (suchas e.g. 85 mm-Hg).

In step 204, it is determined whether the apparatus can detect pulsebeats originating from the pulse point (e.g., the radial pulse pointpalpation mark). If a pulse is detected, then the apparatus will take anaverage of the pulse pressures observed over a specified number of beats(e.g. four (4)), or employ another scheme for obtaining a desired dataset at step 206, and the process will then invoke the simulatedannealing process with average pulse pressure measurements at step 208.If the pulse is not detected, then a “hybrid” lateral process step isinvoked at step 205.

Assuming that a pulse beat has not been detected, the hybrid lateralprocessing step is invoked at step 205. Here, the apparatus will beginlooking for beats by performing a lateral scan beginning at a point thatis a specified distance from the beginning of possible lateral travel.It has been found through experiment that the specified distance oftravel from the beginning of possible lateral travel is often mosteffective at approximately ¼ of an inch (0.25 in.), although more orless travel clearly may be utilized.

Next, the apparatus will “servo” (i.e., continuously orsemi-continuously vary) the applanation position in order to maintain anaverage pressure at a specified position such as e.g. 60 mm-Hg. Duringthe lateral scan, any beats collected by the apparatus are noted alongwith the position and pressure reading of the sensor at the time ofdetection.

At this point in the hybrid lateral process, the apparatus determineswhether it has collected a predetermined number of beats (e.g. four (4)in the illustrated embodiment), or has reached the end of lateral travelwithout detecting the required number of beats. If the end of thespecified lateral travel has been reached without detecting thespecified number of beats, step 205 is repeated; however this time alower lateral scan velocity is used, and/or the possible lateral travelarea is increased.

On the other hand, if the predetermined number of beats had beencollected, the transducer will be positioned over the lateral positionas indicated by the largest reading of the collected beats. At thepoint, the apparatus will servo the applanation position of thetransducer until an average desired pressure (e.g., 85 mm-Hg) isreached, and collect another predetermined number of beats in step 207.

In step 207, if it is determined the hybrid lateral process of step 205was entered into as a result of a motion recovery process; then thenumber of beats collected will be specified at a number such as e.g.twenty (20) collected beats. If not a result of a motion recoveryprocess, a fewer number of collected beats is needed, such as e.g. four(4) beats. The apparatus will then either query whether the requirednumber of beats have been collected in a specified time limit, and ifthe apparatus returns “true” to this inquiry, the apparatus will averagethe pulse pressure measurements collected over the collected number ofbeats and invoke step 208, the simulated annealing process.

If the apparatus times out prior to collecting the specified number ofbeats, then the hybrid lateral process will repeat, but with a lowerscan velocity. If this repeated hybrid lateral process is repeated overa predetermined number of times (e.g. two (2)), then the user will benotified of the processing error, and the process will be terminated ora diagnostic or troubleshooting mode entered if desired.

In step 208, the simulated annealing process is invoked tointer aliaprepare for entry into subsequent dither generation processing steps, asdescribed further below with regards to FIG. 3 and its accompanyingdisclosure. A starting temperature value is selected in step 208 usingthe chart of FIG. 2a showing starting temperature as a function ofinitial pulse pressure. FIG. 2a demonstrates the functional relationshipbetween starting temperature (relative units) selected versus initialpulse pressure (in mm-Hg). For purposes of hardware simplicity, a 1-Dinterpolator may be used to perform a piece-wise linear interpolation ofthe starting temperature versus initial pulse pressure chart of FIG. 2aduring step 208, although more complex interpolations, or curve fittingalgorithms are possible such as e.g. polynomial or even splineinterpolation.

(2) Dither Generation

Referring now to FIG. 3, one exemplary method for dither generation 104is discussed in detail. At a high level, the exemplary dither generationprocess 104 involves three basic steps of operation: (1) determinationof the next dither pair sequence 302; (2) execution of the dither pair316; and (3) clocking the temperature controller 350 according to apre-specified scheme.

Regarding steps (1) and (2), i.e. dither pair determination andexecution, these processing steps will be discussed in detail below withregards to FIGS. 3a, 3b and 3 c.

Regarding step (3), logic within the apparatus will determine whetherthe temperature controller has been clocked a pre-specified (e.g. two(2)) number of times at step 352. If the logic returns “true”, thecurrent temperature will be reduced by by a prescribed amount; e.g., one“click”, at step 356. If the logic returns false, the currenttemperature will be maintained at step 354.

Referring now to FIG. 3a , an exemplary embodiment of the process fordetermining the next dither pair sequence 302 is described in detail. Adither pair sequence determines the order of “experiments” or trialsused when evaluating two different positions for the transducerapparatus. A dither pair sequence can thus be thought of as the center,or “heart” of the simulated annealing process that controls thepositioning of the transducer under this unifying scheme.

In the present embodiment, the dither pair sequence is substantiallyrandomized. The reasoning for this can perhaps best be explained byexample. For instance, imagine that activity with regards to thepatient's pulse pressure is in reality uncorrelated with the apparatusmovements. If this activity involves monotonic changes over largeperiods of time, such as a result of a particular physiological orpharmacological effect, fixing the order of the “experiments” or trialswill have a very predictable and undesirable influence on the testresults. For example, in cases where the patient's pulse pressures aremonotonically increasing, and this increase is such that it is strongerthan any influence exerted by moving the transducer position, thenwhichever position tested last in the dither pair will usually dominate,given that it will have the higher observed pulse pressure (as we aremonotonically increasing in pressure). In such a case the transducerposition would almost never move away from the previously establishedposition. Conversely, if always ending with the dithered position lastin each dither pair, the transducer position would always tend to moveaway with each dither pair to the randomly chosen dither. In order tocombat this effect, the order of the dither pair is randomized,effectively eliminating any long-term accidental and non-causalcorrelation with external pulse pressure changes. Other schemes may beused to avoid such effects as well, however, including those whichspecifically analyze the possible effects (such as the foregoingmonotonic scenario) and adaptively develop a scheme which combats ormitigates such deleterious effects. Furthermore, randomization may notbe required at all times, and hence may be applied selectively ifdesired.

As is known in the mathematical arts, randomizing of signals and/ornumerical sequences is most typically implemented through the use of socalled pseudo random number generators which generate Pseudo RandomBinary Sequences (PRBS). Pseudo Random Binary Sequences (PRBS) are adefined sequence of inputs (+/−1) that possess correlative propertiessimilar to white noise, but converge in within a give time period. Inaddition, the inputs can be specified (and thereby optimized) to producemore effective signal-to-noise ratio (SNR) within the constraints of thesystem. One common type of PRBS sequence generator uses an n-bit shiftregister with a feedback structure containing modulo-2 adders (i.e. XORgates) and connected to appropriate taps on the shift register. Thegenerator generates a maximal length binary sequence according to Eqn.1:maximal length binary sequence=length(2^(n)−1)  (Eqn. 1)The maximal length (or “m-sequence”) has nearly random properties thatare particularly useful in the present invention, and is classed as apseudo-noise (PN) sequence. Properties of m-sequences commonly include:

-   -   (a) “Balance” Property—For each period of the sequence, the        number of ‘1’s and ‘0’s differ by at most one. For example in a        63 bit sequence, there are 32 ‘1’s and 31 ‘0’s.    -   (b) “Run Proportionality” Property—In the sequences of ‘1’s and        of ‘0’s in each period, one half the runs of each kind are of        length one, one quarter are of length two, one eighth are of        length three, and so forth.    -   (c) “Shift and add” Property—The modulo-2 sum of an m-sequence        and any cyclic shift of the same sequence results in a third        cyclic shift of the same sequence.    -   (d) “Correlation” Property—When a full period of the sequence is        compared in term-by-term fashion with any cyclic shift of        itself, the number differences is equal to the number of        similarities plus one (1).    -   (e) “Spectral” Properties—The m-sequence is periodic, and        therefore the spectrum consists of a sequence of equally-spaced        harmonics where the spacing is the reciprocal of the period.        With the exception of the dc harmonic, the magnitudes of the        harmonics are equal. Aside from the spectral lines, the        frequency spectrum of a maximum length sequence is similar to        that of a random sequence.

In step 304, the apparatus will first determine whether in the previousdither pair, did the apparatus both: (1) end with a dithered position;and (2) choose to go towards the dither. In other words, was a newreference position established with the dithered position last. If so,then step 306 is invoked. Conversely, if the answer is no, then step 308is invoked.

Assuming for a moment, that the answer to the logical query of step 304was yes, then step 306 is invoked. At step 306, the apparatus queries todetermine whether the temperature (i.e. the starting temperatureselected at step 208) is low enough to enable an inferred referenceposition. An inferred reference position, as opposed to a standardreference position, is a position that can be extrapolated upon a veryspecific circumstance. This inferred reference position is extrapolatedwhen a new dithered position is tested and the apparatus, and theunderlying algorithm, decides to go towards this new dithered position.

A new reference position, at a predetermined distance between the twopoints beyond the dithered position in a direction that is further awayfrom the previous reference position is “inferred”. In one exemplaryembodiment, this predetermined distance is ⅓^(rd) (33.333%) of theprevious dither. This in effect exaggerates the original dither movementby an additional ⅓^(rd) of the previous dither. However, suchexaggerations are typically only deployed at low temperatures to avoidexcessive movements. At low temperatures this extrapolation isdesirable, as it provides a quantity of gain in order to increase slewrate beyond that which a given dither size would otherwise imply.

FIG. 3d graphically demonstrates for the utility of the aforementionedconcept. Specifically, in cases where there is a fixed applanationdither size, small perturbations cannot be tracked when they are smallcompared to the fixed applanation dither size. Further, with largevariations in the hemodynamic parameter measured, fixed applanationdither sizes may have difficulty in keeping up (i.e. because they aretypically slew-rate-limited) with the signal. Therefore, as can be seenin FIG. 3d , it would be desirable to vary the dither size as a functionof confidence (i.e. by lowering dither size to measure smallperturbations when confidence is high and exaggerating dither size whenconfidence is low as a result of large variations in the signal).

Referring back to step 306, if the temperatures are low enough to enablean inferred reference position, then the apparatus will be asked torandomly choose between either of the following possible dithersequences at step 310: (1) [inferred reference, dither]; or (2) [dither,inferred reference]. Conversely, if the temperatures are not low enough,then the apparatus will randomly choose between either of the followingpossible dither sequences at step 312: (1) [reference, dither]; or (2)[dither, reference].

Referring back to the question queried back at step 304, if the answerto the query at step 304 is negative, then the apparatus will invokestep 308. In step 308, the apparatus queries to determine whether in theprevious dither pair, did we both: (1) end with a reference position;and (2) choose to stay with the reference position (i.e. was a newposition not established and the reference position was last).

If the answer to the query at step 308 is negative, then the apparatuswill randomly choose between either of the following dither sequences atstep 312 as previously discussed.

If the answer is in the affirmative, then the apparatus will chooserandomly either between (1) setting the dither sequence to [dither]; or(2) setting the dither sequence to [reference, dither] at step 314. Inthe case of (1), since a new reference position was not established inthe previous dither pair and the reference position was last, processingtime can advantageously be spared by simply re-using the measurementsfrom the immediately prior measurement position.

Referring now to FIG. 3a (part 2 of 3), one exemplary embodiment of theprocess for executing the dither pair 316 is described in detail. At anabstract level, executing a dither pair according to the presentembodiment is equivalent to reading the specific dither sequencepreviously determined and going to each specified position type insequence. At each position we collect the beat data then move on to thenext position specified in the sequence. At the conclusion of thisiterative data collection enough data has been collected to make adecision on which position should be declared as our reference position.

At step 318, the next position type specified in the sequence is firstqueried to determine what position type it is. Depending on its positiontype, different algorithms or processing steps may be implemented inorder to process and execute the respective dither pair. If the positiontype is an inferred reference position, then step 320 is invoked, whileif it is a reference position or dithered position, steps 322 or 324 areinvoked, respectively.

At step 320, the position type has been determined to be an inferredreference position by the apparatus. The reference position and the nexttarget are set to a position that is a predetermined value (e.g. ⅓^(rd))as far as the difference between the previous reference position and theprevious dithered position beyond the previous dithered position.Mathematically, if our previous positions are designated P_(Reference)_(i-1) and P_(Dither) _(i-1) then the new reference positionP_(Reference) _(i) is computed as follows using Eqn. 2:

$\begin{matrix}{P_{{Reference}_{i}} = {P_{{Dither}_{i - 1}} + \frac{P_{{Dither}_{i - 1}} - P_{{Reference}_{i - 1}}}{3}}} & \left( {{Eqn}.\mspace{14mu} 2} \right)\end{matrix}$If the position type has been determined to be a reference position,then the apparatus will set the target position to the current referenceposition at step 322.

If the position type has been determined to be a dithered position, thena dithered position is generated at step 324, requiring the generation,transformation and “baking” of a “unit dither” at step 326. The term“baking” refers in the present context to the process of modifying thevalue of the unit dither as a function of temperature. At step 324, theapparatus must first determine the axes that will be involved in thedither. These axes may include, but are not limited to, the Cartesianaxes previously discussed (i.e. applanation, lateral, and distal axes).In one exemplary implementation, each dither can utilize movements inany combination of the actuator axes (i.e., the aforementionedapplanation, lateral and distal axes) either serially or in parallel.The ability to move in more than one axis in parallel can potentiallyspeed up the response for cases where the pulse pressure profiles are atsteep angles with respect to the principle axes. However, for pulsepressure profiles that are largely parallel with the principle axes,single axis moves are often more beneficial. It is believed that most ofthese profiles are largely parallel, but not exactly parallel to, theprinciple axes. For purposes of robustness to alternate pulse pressureprofiles, while at the same time acknowledging the nominal tendency forthe profiles to be largely parallel to the exemplary actuator axes, arandom mix of single and multiple axes dithers are performed in theillustrated embodiment, whose distribution is statistically controlledas a function of the current temperature.—

At step 328, and in one exemplary embodiment, a 1-D interpolator is usedto perform a piece-wise linear interpolation of the chart shown at FIG.3e to determine the applanation axis only dither probability. Thisexemplary chart shown in FIG. 3e is constructed currently such that athigh temperature values, the chart returns a value of 0.33, while at lowtemperature values it returns a value of 0.66. Thus in this example,applanation-only dithers are twice as probable at low temperaturevalues, than at high temperature values. The remaining dithers will beequally divided between performing a lateral-only dither, or a combinedapplanation and lateral dither, etc. A substantially random number isgenerated in the closed interval [0, 1]. This random number is thentested, if the random number is less than the applanation-onlyprobability, then only applanation will be involved in the next dither.If the random number is greater than or equal to the applanation-onlyprobability; and is less than Eqn. 2, then only lateral movements willbe involved in the next dither. If the random number is greater than orequal to Eqn. 3, then both applanation and lateral movements will beinvolved in the next dither.

$\begin{matrix}{1 - \left( \frac{1 - {{applanation\_ only}{\_ probability}}}{2} \right)} & \left( {{Eqn}.\mspace{14mu} 3} \right)\end{matrix}$

Referring now to FIG. 3b , the unit dither is generated, transformed and“baked”. A unit dither is a unit less ordered N-Tuple of numbers, eachof which is from the closed interval [−1, 1], with N being the number ofaxes of movement implemented in the exemplary actuator context. ThisN-Tuple of numbers is central to the process for generating randomizeddithers for the simulated annealing algorithm described herein. Forpurposes of simplicity, it is assumed that the number of axes (N) in theexample of the process of step 326 is equal to two (2), although more orless axes may be incorporated.

At step 330, the unit dither is generated. The apparatus firstdetermines whether the unit dither generation is for a reference dither.If the result returns “true”, then a unit dither of [0, 0] will bereturned. If the result returns “false”, then a randomly generatedN-Tuple that resides in a unit cube is generated. Unit dither generationis first started by generating a random point within the unit cube.Although it is not desirable to end up with a unit sphere, using aspherical coordinate system to generate the random point will allow fora distribution of points such that most of the points will beconcentrated at small radii. Random spherical generation will distributepoints in such a way that the number of points at a given radius isnominally constant, thus this would imply lower densities at higherradii, as this constant number of points will be distributed over alarger circumference at the larger radii. To avoid this situation,random points are first generated in a Cartesian coordinate system, ineffect guaranteeing a uniform distribution of points per unit volume.

Generating a randomly generated N-tuple is accomplished in one exemplaryembodiment in the following manner. These steps are repeated for each ofthe N dimensions, here two (2), to generate the N-tuple.

First, a signed random number in the closed interval [−1, 1] isgenerated. Next, the concept of offset bias is introduced. Adaptive andaxis-specific offset biases, each of which are constrained to values inthe closed interval [−1, 1], are maintained to influence thedistribution of the randomly generated dithers. For example, a ditheroffset bias value of zero in the illustrated embodiment indicates thatthere is no bias applied to the given dither generation for a givenaxis, while a value of 1.0 indicates that 100% of the time a positivegoing dither will be generated. Likewise a dither offset value bias of−1.0 indicates that 100% of the time a negative going dither will begenerated. This concept is utilized to adaptively respond to evidencedeveloped that indicates, for example, that the majority of successfuldithers in the recent positioning history along the applanation axiswere mostly negative. In this case, a negative dither offset bias willbe generated to increase the likelihood of generating negativeapplanation dithers.

Using the current adaptively-determined offset bias for the givendimension i, Bias_(i). Bias_(i) is clipped to the closed interval of[−0.99, 0.99]. Bias is then calculated as being equal to 1 minus Bias. Arandom number R is generated in the closed interval [0, 1.0] and then asigned random number is calculated using Eqn. 4.SignedRandomNumber=2×R−Bias  (Eqn. 4)If SignedRandomNumber is greater than zero, then Eqn. 5 is used; if itis less than zero, Eqn. 6 is used. The i^(th) component of the N-Tupleis set to the newly calculated SignedRandomNumber.SignedRandomNumber=SignedRandomNumber×1.0÷(2.0−Bias)  (Eqn. 5)SignedRandomNumber=SignedRandomNumber×1.0÷Bias  (Eqn. 6)

The unit dither specification is then tested for compliance. The radiusof the unit dither is computed, and exemplary logic determines whetherthe radius of the unit dither is less than or equal to one, to ensurethat the point falls inside of the unit sphere. If the unit dither fallswithin the unit sphere, then the logic determines if the radius isgreater than or equal to 0.5. This test is utilized to avoid thegeneration of small dithers relative to the maximum possible given thecurrent temperature.

If greater than or equal to 0.5, the square of the radius is calculated,while either serially or in parallel a random number is generated in theclosed interval [0, 1]. If the random number generated is less than orequal to the square of the radius, then the unit dither passes thecriteria established and the result is returned. If any of these testsfail, unit dither generation is repeated.

In step 332, the unit dither is transformed to a number with physicalunits to guide the actuator movement. The transformation processconverts this unit less N-tuple into a similar N-tuple, but withphysical units. Note, however, that the units may be different dependingon the axis that it controls. For instance applanation units in thetransformed unit dither may be in mm-Hg, although this is by no means arequirement, thus allowing for a tissue compliance-related responsefurther downstream in the apparatus code. Similarly units for lateralposition may use finer units than that used for distal position, toaccount for differences in the potential range between these two axes.It is in this step that nominal differences in travel, i.e. aspectratio, between the various axes are taken into account.

First, for each axis in the N-tuple of the unit dither specification,the axis-specific component in the N-tuple will be transformed. Themaximum specified dither travel for the given axis Dither_(max) _(i)will then be obtained. In one embodiment, this quantity will be fixed atthe compile time of the software implementing the algorithm, and willrepresent the nominal maximum dither to be generated for the given axis,though run-time adaptations can cause the generations of yet largerdithers when determined to be appropriate. The i^(th) component of theN-tuple is then transformed into physical units using Eqn. 7.Dither_(i)=Dither_(max) _(i) ×Unit_dither  (Eqn. 7)

The adaptively determined aspect ratio is then applied. “Aspect ratio”as used in the context of the present embodiment specifically refers tothe aspect ratio between the applanation and lateral and/or distal axes,etc., however for simplicity it will be only discussed as the ratiobetween applanation and lateral. In this particular embodiment, thismore specifically refers to the ratio of the maximum applanation ditherto the maximum lateral dither (or derivative quantities relatingthereto). At compile-time, a fixed nominal aspect ratio is defined suchthat a given unit dither specification of [1, 1], the resulting ditherwill have an applanation displacement versus a lateral displacement thatare related by this nominal aspect ratio. In other words, the nominalaspect ratio defined at compile-time allows the code to abstract thesenominal differences away, and therefore can largely concentrate insteadon the run-time tweaks to this basic relationship.

An aspect ratio “tweak” in the present context is an adaptivelydetermined quantity that is signed and has values in the closed interval[−1, 1]. A value of “0” implies that no adaptation is necessary in thedither aspect ratio. A positive value indicates that over-and-above thenominal aspect ratio, applanation should be further emphasized, and anegative value indicates that lateral should be further emphasized. Inactual implementation when, e.g., an applanation emphasis is called for,(i.e. an aspect ratio “tweak”>0), “half” of this emphasis is placed uponthe applanation axis, and “half” of this is used to de-emphasize thelateral axis. In this way, disruptions resulting from too large a degreethe nominal vector length of the dither being generated areadvantageously avoided. If for instance, the applanation axis has anaspect ratio tweak value that is positive, the applanation dither isfurther emphasized. Note also that the use of “half” of the aspect ratiotweak on the applanation axis, and the other half on the lateral axis ismeant purely in a geometric sense; hence the use of the square root inEqn. 8. The invention is in no way limited to such “half” or otherschemes, however. Conversely, if the applanation axis has an aspectratio tweak value that is negative, Eqn. 9 is used which effectivelyde-emphasizes further the applanation dither.

$\begin{matrix}{{Dither}_{i} = {{Dither}_{i} \times \sqrt{1.0 + {{{aspect\_ ratio}{\_ tweak}}}}}} & \left( {{Eqn}.\mspace{14mu} 8} \right) \\{{Dither}_{i} = {{Dither}_{i} \times \frac{1}{\sqrt{1.0 + {{{aspect\_ ratio}{\_ tweak}}}}}}} & \left( {{Eqn}.\mspace{14mu} 9} \right)\end{matrix}$An adaptively determined aspect ratio adjustment for pulse pressurecurve asymmetry is then applied. This is done in order to account forthe typical pulse pressure curve asymmetries found irrespective ofwhether the device is currently operating above or below the patient'smean pressure. It has been found by the inventors hereof that pulsepressure slopes above the patient's mean pressure roll-off at a muchsteeper rate than the pulse pressure rise below the patient's meanpressure. In other words, when above the patient's mean pressure, thereis a need to de-emphasize the applanation axis dither, while this dithershould be emphasized when below the patient's mean pressure.

The adaptively determined dither offset values can be utilized to givean indication whether or not the apparatus is largely applanating orde-applanating. If the apparatus is largely applanating, then it can bededuced that pulse pressure readings may be below the patient's meanpressure. Conversely, if the apparatus is largely de-applanating, thenit is likely that the readings are above the patient's mean pressure.Through studies conducted by the Assignee hereof, it has been determinedthat this ratio is roughly 260%; that is, the pulse pressure slopes areapproximately 2.6 times steeper above the patient's mean than below it.Therefore, given AboveVsBelowMeanPPRatio=2.60, the application ratiotweak is calculated using Eqn. 10 where the AppOffset value is greaterthan or equal to zero, otherwise Eqn. 11 is used.

$\begin{matrix}{{AppTweak} = \frac{1}{1 + {\left( {\sqrt{AboveVsBelowMeanPPRatio} - 1} \right) \times {{AppOffset}}}}} & \left( {{Eqn}.\mspace{14mu} 10} \right) \\{{AppTweak} = {1 + {\left( {\sqrt{AboveVsBelowMeanPPRatio} - 1} \right) \times {{AppOffset}}}}} & \left( {{Eqn}.\mspace{14mu} 11} \right)\end{matrix}$Thus, the dither value at each position i is calculated using the valueobtained by either Eqn. 10 or Eqn. 11 using Eqn. 12.Dither_(i)=Dither_(i)*AppTweak  (Eqn. 12)Similarly, if it is desired to de-emphasize (using Eqn. 13) or emphasize(Eqn. 14) other axes, such as the lateral axis, this can be calculatedas well using similar aspect ratio tweaks.

$\begin{matrix}{{Dither}_{i} = {{Dither}_{i} \times \frac{1}{\sqrt{1.0 + {{{aspect\_ ratio}{\_ tweak}}}}}}} & \left( {{Eqn}.\mspace{14mu} 13} \right) \\{{Dither}_{i} = {{Dither}_{i} \times \sqrt{1.0 + {{{aspect\_ ratio}{\_ tweak}}}}}} & \left( {{Eqn}.\mspace{14mu} 14} \right)\end{matrix}$

Following the transformation process of the unit dither, the unit ditheris now “baked” at step 334. The term “baking” refers in the presentcontext to the process of modifying the value of the unit dither as afunction of temperature. It is generally expected that a response athigh temperatures (i.e. correlating to a lower confidence that thetransducer is located properly) the system should be displaced more,while at lower temperatures the system is expected to be displaced less.

In one embodiment, the transformed unit dither is baked by firstobtaining the current “taxed” temperature for each axis. “Taxing”, asthe name implies, is the core system temperature with an added “tax”;here a generic and arbitrary quantity that can be used for multiplepurposes. A tax can be applied to the temperature for various reasons,but in general it is used to penalize the system, or perhaps put it inan increased state of perturbation or awareness. In this embodiment, thetemperature is taxed only when the current mean pressure is particularlyhigh or low (as determined against, e.g., predetermined or variantcriteria), corresponding to the likelihood that the value is notcorrect.

It should also be noted that in the current embodiment, a temperaturecan be used either taxed or not taxed and thus at any one time bothversions can be made available in the system. In an alternateembodiment, each axis will have a temperature equivalent to thesystem-wide core temperature.

Referring now to FIG. 3f , the temperature coefficient is determinedusing a 1-D interpolator to perform a piece-wise linear interpolation ofthe chart depicted in FIG. 3f . The baked dither is then calculatedusing Eqn. 15.Dither_(i)=tempco×Dither_(i)  (Eqn. 15)

Referring again back to FIG. 3a (part 3 of 3), in step 336 the apparatusadvances to the target position, regardless of whether it was aninferred reference position, reference position or a dithered position.If the target position is not reached within a predetermined amount oftime (e.g. 1.5 seconds), then the system times out on this dither andnotifies the system while aborting the simulated annealing process.

If the target position is reached in time, the beat data is collected atstep 338. The process for collecting beat data is described in detailbelow with regards to FIG. 3c and its accompanying disclosure.

After collection of the beat data, the system determines whether thelast position was the last position type in the sequence at step 346. Ifit is not, the whole process repeats starting at step 318. If it is thelast position in the sequence, the algorithm advances to hemodynamicparameter processing.

(3) Hemodynamic Parameter Processing

Referring now to FIG. 3c , the collection of beat data 338 is describedin detail. At step 340, the number of beats to collect is determined. Inone embodiment, the number of beats to collect is fixed at apredetermined number (e.g. two (2)). Alternatively, in a secondembodiment, the number of beats is collected as a function of one ormore parameters (e.g., temperature). In this example, a piece-wiselinear interpolation of the chart of FIG. 3f (Temperature vs. Beats toCollect) is used to determine the baseline number of beats to becollected.

In a third embodiment that can be used either alone or in conjunctionwith either of the two previous embodiments, (computer or algorithmic)logic determines whether the core temperature value is below a certainthreshold (e.g. 2000). If so, then a statistical algorithm is employedwhich first generates a random number in the closed interval [0, 1] andtests this random number to see whether it is either higher or lowerthan the midpoint of the interval (i.e. 0.5). If it is less than themidpoint, a pre-specified number of beats are added (e.g. one (1)),while if the random number is greater than the midpoint, the number ofbeats to detect is left at the existing value.

The reason for the foregoing approach utilized in this third embodimentis that at low temperatures, there are conflicts between two opposingneeds. As the vast majority of dithers will occur at lower temperatures,the decisions made at these low temperatures would benefit by as littlenoise as is practicable. On the other hand, it is undesirable tosacrifice a rapid response to large changes, and to a large degree thenoise is taken out in the long run as the results of consecutive dithersthat are cumulative in nature.

Furthermore it has been observed that at low temperatures, the resultantdithers of these decisions are small in nature and that they thereforedo not by themselves have a large impact on these decisions. So inresponse, an approach is taken that statistically adds in the equivalentof an additional “half a beat” on average at these low temperatures.

Therefore, at these lower temperatures, half of the time the number ofbeats are taken as normally would be determined given the currenttemperature, etc., and the other half of the time, one additional beatis taken under this third embodiment.

At step 342, beat detection is delayed for a predetermined amount oftime. This beat delay detection is utilized to account for delays suchas (1) group delays in batch processing; or (2) for settling time aftera dither. In one embodiment, these delays are set to 250 ms and 125 msrespectively, accounting for a total delay of 375 ms, although it willbe recognized that other values may be used.

At step 344, the apparatus waits for either a beat timeout or a detectedbeat. A beat timeout in the present context comprises the absence of adetected beat during any designated epoch of time, such as e.g., five(5) seconds. While primarily envisioned as only utilizing apre-established epoch of time, certain embodiments of the presentinvention may extend, contract or adapt this timeout as conditionschange within the system. For example, after a detected motion event,the wait period may be reset, re-establishing the full designated epochof time. Alternatively, after a detected motion event, the wait periodmay be extended for a specified period of time.

If on the other hand a beat is detected, the exemplary apparatusexecutes logic which determines whether the detected beat occurredwithin a prescribed period (e.g., one second) of a previously detectedmotion event. If it has, then the beat is ignored. If not, the beat isstored for later processing. For example, in one embodiment, thedetected beat is added to previously detected beats to keep a runningaverage calculation of mean pulse pressure values over the duration ofthe beat collection cycle.

Referring now to FIG. 4, the hemodynamic parameter processing step 106of FIG. 1 is described in detail.

At step 400, patient monitoring mode (PMM) bias is applied to themeasured pulse pressure difference. PMM bias is a correction that isapplied to the measured pulse (pulsatile) pressure difference in orderto correct what has been observed as flat pulse pressure curves. It hasbeen observed through experiment by the Assignee hereof that when thepulse pressure versus mean pressure curves becomes flattened, the peakin this curve occurs at a place that is actually higher than thepatient's mean pressure. The flatter the curve becomes, the larger thisoffset appears to be. As the peak in this pulse pressure curve is usedas a basis to determine the patient's mean pressure, a corrective biasis applied in order to shift the peak towards lower pressure to correctfor this phenomenon. This shift is such that it will typically be largerfor flatter curves, and smaller for sharper curves. In one embodiment,this factor has been set to 35% (0.35). However, in order to avoidissues of these bias values lowering pressures too far, various measuresare taken to curtail its effect. In one exemplary embodiment, the PMMbias in step 400 is applied as follows using Eqn. 16 and Eqn. 17:ΔPP=PP_(dither)−PP_(ref)  (Eqn. 16)ΔMean=Mean_(dither)−Mean_(ref)  (Eqn. 17)

After performing these two calculations, the PMM bias is determined byperforming a piece-wise linear interpolation of the reference mean as afunction of PMM bias (chart shown in FIG. 4a ) to determine the nominalPMM bias to use. This linear interpolation can be performed by using aninterpolator (e.g. a 1-D interpolator). After obtaining the currenttaxed (or in some embodiments, untaxed) temperature, a piece-wise linearinterpolation of the temperature as a function of PMM bias temperaturefactor is determined using a chart such as that shown in FIG. 4b . Theaddition of the pulse pressure bias is then performed thusly using Eqn.18, Eqn. 19 and Eqn. 20:PMMBias_(compsite)=PMMBias_(nominal) ×k _(temp)  (Eqn. 18)PP_(bias)=−ΔMean×PMMBias_(composite)  (Eqn. 19)Note that the term on the right side of Eqn. 19 is negative to reflectthat the higher the mean pressure difference is, the more the pulsepressure difference should be de-emphasized.Clip PP_(bias) to the closed interval [−1.2,1.2] mm-Hg; andCalculate ΔPP=ΔPP+PP_(bias)  (Eqn. 20)Next, the algorithm must make the transition decision at step 402. Thistransition decision is based on a combination of where the timeoutoccurred, and in which position (dithered and/or reference). If notimeout occurred in either position (i.e. dithered and reference), whichis the most typical case, then pulse pressure change is determined usingEqn. 21 at step 406.PP_(change)=PP_(dither)−PP_(reference)  (Eqn. 21)

At step 408, the transition probability is determined. In simulatedannealing, transition probabilities are based upon both the change inenergy, (the negative of the change in pulse pressure in oneembodiment), and the current temperature. While the transitionprobability is normally set to 100% if there is a decrease in energy,(simulated annealing attempts to lower the total energy of a system;this is equivalent to an increase in pulse pressure in the exemplaryimplementation for a hemodynamic system), there are a variety ofresponses for the cases of no change in energy, or for an increase inenergy state. This feature in large part gives simulated annealing itsinherent ability to be able to move away from locally optimal areas andfind what would be the global optima. In essence, it is the ability tooccasionally, in a metered way and under strict control, advance a movetowards a higher energy (lower pulse pressure) state, that provides manyof the benefits of the simulated annealing control process.

In step 408, the change in energy is determined using a piece-wiselinear interpolation of the ΔEnergy as a function of ΔPressure (seechart of FIG. 4c ). Note that the chart and linear interpolation areonly used for changes of pulse pressure that are negative. If theΔEnergy is negative, the transition probability is set to 1.0. If theΔEnergy is equal to zero, then the transition probability is set to 0.5.If the ΔEnergy is positive (i.e., the dithered position resulted in asmaller pulse pressure) and the current temperature is greater than aprescribed value (e.g., 500), then the transition probability is set tozero. However, if the ΔEnergy is positive and the current temperature isless than 500, then a 2-D interpolator is used to perform a bi-linearinterpolation of the transition probability as a function oftemperature, and the delta energy chart of FIG. 4c is utilized todetermine the transition probability.

At step 410, if the timeout was only in the dithered position, or was inboth the reference and dithered positions, then the transitionprobability is set to zero. Conversely, at step 412, if the timeout onlyoccurs in the reference position, then the transition possibility is setto 1.0.

At step 414, a decision is made about whether to take the transition ornot. In one embodiment, the apparatus will generate a random number inthe closed interval [0, 1]. If the random number is less than thetransition probability then the system will take the transition towardsthe dithered position, otherwise it will start with the currentreference position.

(4) Adaptive Behavior

Referring now to FIG. 5, an exemplary embodiment of the adaptiveadjustment algorithm of the invention is described.

Per step 500 the temperature is adaptively adjusted. Note that theexemplary adjustments described herein are subject to limits beyondwhich the adjustment will not take effect. For temperature increases,the limit imposes a maximum, and for temperature decreases, the limitimposes a minimum. In adjusting the temperature, the timeout pattern isalso analyzed. In the nominal case (i.e. where there is no timeout),signs of excessive modulation of the pulse pressure are identified bydetermining whether or not there was a large pressure change (step 502).In one exemplary embodiment, this determination is accomplished in atwo-step process. First, logic determines whether the large pulsepressure is greater than a prescribed value (e.g., fifteen (15) mm-Hg).If not, the logic returns “false”; otherwise logic then queries whetherthe smaller pulse pressure is less than or equal to a given percentage(e.g., 60%) of the larger pulse pressure. If it is, then the logicreturns “true”, otherwise it returns “false”. While the threshold limitsof fifteen mm-Hg and 60% of the larger pulse pressures have been chosenfor this example, it is understood that these numbers may varyconsiderably from application to application, the aforementioned numbersmerely being exemplary.

If the pressure change was too large in magnitude (i.e., the logic hasreturned true), then the temperature is reduced (e.g. by a prescribedincrement such as 2 “clicks”) at step 504. If there was not a largeinstant pressure change, logic then determines whether or not there wasa large mean pressure change to determine whether the mean pressure isbeing excessively modulated. In one embodiment, if the mean pressurechange increases by more than 35 mm-Hg, then the logic will return“true” and the temperature will be decreased by a set amount (e.g. two(2) clicks). If not, then logic determines if there was too small of apulse pressure or mean pressure change at step 506. This is to ensurethat at least a minimal amount of both pulse pressure and mean pressuremodulation is applied to the system.

In one variant, if the absolute pulse pressure change is less than 1mm-Hg, then the logic will return “true”, otherwise it will determine ifthe absolute mean pressure change is less than 1.5 mm-Hg, and thenreturn “true” if the answer is yes, otherwise it will return “false”. Iflogic determines the change was too small, then the temperature isincreased at step 510 (e.g. by 1.3 clicks), otherwise the temperature iskept current (step 508).

Note however that the aforementioned process (i.e. steps 502-510) areapplicable when there has been no timeout observed. At step 512, logicdetermines whether there was a dither beat timeout, a reference beattimeout, or both. At step 514, the occurrence of a dither beat timeoutevent normally suggests that the system may have been dithered too muchso as to lose the beat at the dithered position. This suggests atemperature that is too high if the assumption that has been made iscorrect. However, if the reference beat is not strong either, then thereis a risk of losing the reference beat as well by dithering too much,and inducing too much large signal behavior.

Therefore, before assuming that the initial assumption was a valid one,logic is used in the exemplary algorithm to determine whether thereference beat pulse pressure is greater than a minimum amount (e.g. 10mm-Hg), which is to ensure that reducing temperature does not raise thepossibility that the reference beat may be lost by any large temperaturechanges to the system. If the reference beat pulse pressure is greaterthan the minimum amount, then the temperature is decreased. In oneexemplary embodiment, the temperature is reduced by three (3) clicks,otherwise no change is made.

At step 516, if there was only a reference beat timeout, then thetemperature is increased. In one embodiment, this temperature increaseis 1.5 clicks, although other values may be used.

At step 518, if there is both a reference and a dither beat timeout,then the temperature is increased. In one embodiment, this temperatureincrease is by 2.5 clicks. Note that in the illustrated embodiment, thetemperature increase for this second condition (both timeouts) is largerthan for the reference-only timeout, since greater correction magnitudeis ostensibly required.

At step 519, respective dither strengths are determined given the ditherspecification. Dither strength is a characterization of the degree towhich a particular dither was deemed to be either strongly lateral orstrongly applanation, etc., or alternatively the degree to which it wasstrongly neither. Recall that in general, random dithers have been takenalong all of the participating axes, however in order to tune variousadaptive parameters it is often important to collect data on theeffectiveness of the dithers taken primarily along one of the principleaxes. In one embodiment, a strong predominantly signal-axis dither istaken to be one whereby its normalized dither, equivalent to its mappingin the unit sphere, is within 30 degrees of a principle axis. In oneexemplary embodiment, the dither strength is determined as follows:

Step One: Normalize the applanation and lateral dither amounts usingEqn. 22;

$\begin{matrix}{{k_{app} = \frac{{Dither}_{app}}{{Dither}_{\max_{app}}}};{{{and}\mspace{14mu} k_{lat}} = \frac{{Dither}_{lat}}{{Dither}_{\max_{lat}}}}} & \left( {{Eqn}.\mspace{14mu} 22} \right)\end{matrix}$

Step Two: If k_(app)=0 and k_(lat)=0, return neutral, otherwise;

Step Three: Test the lateral dither amount using Eqn. 23k _(lat) ²≤0.25×(k _(app) ² +k _(lat) ²)  (Eqn. 23)

Step Four: If yes to step three, then test Dither_(app)>0. If yes,return App_Is_Strongly_Positive, otherwise returnApp_Is_Strongly_Negative;

Step Five: If no to step three, then test the applanation dither amountusing Eqn. 24k _(app) ²≤0.25×(k _(app) ² +k _(lat) ²).  (Eqn. 24)

Step Six: If yes to step five, then test Dither_(lat)>0. If yes, returnLat_Is_Strongly_Positive, otherwise return Lat_Is_Strongly_Negative; Ifno to step five, then return neutral.

At step 520, a 12-point running sum for both applanation and lateralmovements is recorded.

It will be recognized that while the foregoing process is described withrespect to lateral and/or applantion axes or dimensions, others may beused, either in place of the foregoing, or in conjunction therewith (oreven in different permutations), as will be readily implemented by thoseof ordinary skill given the present disclosure.

At step 522, the applanation and running sums for the adaptations areupdated. In a first embodiment, these sums are updated as follows.

If App_Is_Strongly_Positive is returned, then logic determines whetherthe transition to the dither was taken. If yes, the applanation runningsum is fed a value of two (2), otherwise it is fed a value of negativeone (−1).

If App_Is_Strongly_Negative is returned, then logic determines whetherthe transition to the dither was taken. If yes, the applanation runningsum is fed a value of negative two (−2), otherwise it is fed a value ofone (1).

If Lat_Is_Strongly_Positive is returned, then logic determines whetherthe transition to the dither was taken. If yes, the lateral running sumis fed a value of two (2), otherwise it is fed a value of negative one(−1).

If Lat_Is_Strongly_Negative is returned, then logic determines whetherthe transition to the dither was taken. If yes, the lateral running sumis fed a value of negative two (−2), otherwise it is fed a value of one(1).

If nothing is returned, nothing is added to the running sums.

At step 524, the adaptive aspect ratio is determined. First, however, asimilarity score that measures how similar the applanation and lateralvalues are, a dissimilarity score that determines how dissimilar theapplanation and lateral values are and the categorization strength scorethat measures the extent to which the similarity and the dissimilarityscores can be trusted needs to be determined. The equations for thesecalculations are shown below as Eqn.'s (25) through (28).

$\begin{matrix}{{{Score}_{app} = \frac{{RunningSum}_{app}}{24}};{{{and}\mspace{14mu}{Score}_{lat}} = \frac{{RunningSum}_{lat}}{24}}} & \left( {{Eqn}.\mspace{14mu} 25} \right) \\{{{Score}_{similarity} = 1.0},{_{{Score}_{app} = {{{0\&}{Score}_{lat}} = 0}}\frac{{Min}\left( {{{Score}_{app}},{{Score}_{lat}}} \right)}{{Max}\left( {{{Score}_{app}},{{Score}_{lat}}} \right)}}_{otherwise}} & \left( {{Eqn}.\mspace{14mu} 26} \right) \\{{{Score}_{dissimilarity} = 0.0},{_{{Score}_{app} = {{{0\&}{Score}_{lat}} = 0}}\frac{{{Max}\left( {{{Score}_{app}},{{Score}_{lat}}} \right)} - {{Min}\left( {{{Score}_{app}},{{Score}_{lat}}} \right)}}{{{Score}_{app}} + {{Score}_{lat}}}}} & \left( {{Eqn}.\mspace{14mu} 27} \right) \\{{Score}_{categorization\_ strength} = \frac{{{Max}\left( {{{Score}_{similarity}},{{Score}_{dissimilarity}}} \right)} - {{Min}\left( {{{Score}_{similarity}},{{Score}_{dissimilarity}}} \right)}}{{{Score}_{similarity}} + {{Score}_{dissimilarity}}}} & \left( {{Eqn}.\mspace{14mu} 28} \right)\end{matrix}$

Next, if the variable Score_(categorization) _(_) _(strength)≥0.35 thenlogic determines whether or notScore_(dissimilarity)>Score_(similarity). If not, then the scores aresaid to be too unequivocal or indefinite, and hence cannot be actedupon. In this case, the aspect ratio will be slowly decayed towardszero, which is generally the safest place to be whenever in doubt. Inone embodiment, the aspect ratio is thus calculated using Eqn. 29:k _(AspectRatio)=0.85×k _(AspectRatio)  (Eqn. 29)If however, the parameter Score_(categorization) _(_) _(strength)≥0.35,but Score_(dissimilarity)<Score_(similarity), then this is an indicationthat the scores are probably similar. The aspect ratio should thus beaffected by the confidence of a similarity, however to be more careful,the aspect ratio is approached geometrically rather than by making asudden change to a new value. Recall that our target aspect ratio for asimilarity is simply towards zero. The aspect ratio is thus in oneembodiment calculated as:k _(AspectRatio)=0.4×k _(AspectRatio)  (Eqn. 30)If Score_(categorization) _(_) _(strength)≥0.35 andScore_(dissimilarity)>Score_(similarity), then this is an indicationthat the scores are probably dissimilar. However, this is obviously easyto conclude when one of the scores (e.g. applanation or lateral) is 0.So it must also be demanded in that case a minimum absolute differenceof scores (see e.g. Eqn. 31).(Score_(applanation)≠0andScore_(lateral)≠0); or(∥Score_(applanation)|−|Score_(lateral)∥>0.08)  (Eqn. 31)If Eqn. 31 is satisfied, then the likelihood of dissimilarity is moreconfidently reaffirmed. However, the case where one of the scores(applanation or lateral) is zero has not been ruled out. Since such acondition tends to exaggerate the dissimilarity score, when such a caseoccurs it is desirable to modulate the dissimilarity score by themagnitude of the non-zero score. See Eqn. 32.Score_(dissimilarity)=Min(1.0,4*Max(Score_(applanation),Score_(lateral)))*Score_(dissimilarity)  (Eqn.32)If Score_(dissimilarity)>Score_(similarity), then the aspect ratio iscalculated in one embodiment using Eqn. 33, otherwise no action istaken.k _(AspectRatio) =k _(AspectRatio)+0.6×(4×Score_(Dissimilarity) −k_(AspectRatio))  (Eqn. 33)

At step 526, a temperature tax is adaptively assessed upon the referencemean. First, the latest reference mean is added to an n-point (e.g.5-point) running average. In one embodiment, the balance of thesecalculations occurs upon demand at the time that the taxed temperatureis required. This is particularly advantageous, as the tax is based uponthe current core temperature at the time that it is needed.

Next, a piece-wise linear interpolation is performed on an average meanas a function of temperature tax chart as is shown in FIG. 5a . Upondetermining the temperature tax, logic determines if an “alternativeminimum tax” (AMT) should be assessed. This AMT is assessed whentemperatures go below a certain threshold. This logic asks whether ornot the core temperature is below MaxTempForAMT? If so, then use Eqn.34, otherwise the apparatus uses Eqn. 35.

$\begin{matrix}{{EffectiveTemp} = \frac{\left( {{CoreTemp} + {MaxTempForAMT}} \right)}{2}} & \left( {{Eqn}.\mspace{14mu} 34} \right) \\{{EffectiveTemp} = {CoreTemp}} & \left( {{Eqn}.\mspace{14mu} 35} \right)\end{matrix}$The taxed temperature is then calculated using Eqn. 36.TaxedTemp=EffectiveTemp×TemperatureTax  (Eqn. 36)System Apparatus for Hemodynamic Assessment

Referring now to FIG. 6, exemplary embodiments of apparatus formeasuring hemodynamic properties within the blood vessel of a livingsubject consistent with the control methodologies of the presentinvention are now described. In the illustrated embodiment, theapparatus is adapted for the measurement of blood pressure within theradial artery of a human being, although it will be recognized thatother hemodynamic parameters, monitoring sites, and even types of livingorganism may be utilized in conjunction with the invention in itsbroadest sense.

The exemplary apparatus 600 of FIG. 6 fundamentally comprises anapplanation assembly (including one or more pressure transducers 622)for measuring blood pressure from the radial artery tonometrically; adigital processor 608 operatively connected to the pressuretransducer(s) 622 (and a number of intermediary components) for (i)analyzing the signals generated by the transducer(s); (ii) generatingcontrol signals for the stepper motor 606 (via a microcontroller 611 aoperatively coupled to the stepper motor control circuits); and (iii)storing measured and analyzed data. The motor controllers 611, processor608, auxiliary board 623, and other components may be housed eitherlocally to the applanator 602, or alternatively in a separatestand-alone housing configuration if desired. The pressure transducer622 and its associated storage device 652 are optionally made removablefrom the applanator 602.

The pressure transducer 622 is, in the present embodiment, a strain beamtransducer element which generates an electrical signal in functionalrelationship (e.g., proportional) to the pressure applied to its sensingsurface, although other technologies may be used. The analog pressuresignals generated by the pressure transducer 622 are converted into adigital form (using, e.g., an ADC 609) after being optionally low-passfiltered 613 and sent to the signal processor 608 for analysis.Depending on the type of analysis employed, the signal processor 608utilizes its program either embedded or stored in an external storagedevice to analyze the pressure signals and other related data (e.g.,stepper motor position as determined by the position encoder 677,scaling data contained in the transducer's EEPROM 652 via I2C1 signal).

As shown in FIG. 6, the apparatus 600 is also optionally equipped with asecond stepper motor 645 and associated controller 611 b, the secondmotor 645 being adapted to move the applanator assembly 602 laterallyacross the blood vessel (e.g., radial artery) of the subject asdescribed above. A third stepper motor (not shown) and associatedcontrols may also be implemented if desired to control the proximalpositioning of the applanation element 602. Operation of the lateralpositioning motor 645 and its controller 611 b is substantiallyanalogous to that of the applanation motor 606, consistent with themethodologies previously described herein.

As previously discussed, continuous accurate non-invasive measurementsof hemodynamic parameters (e.g., blood pressure) are highly desirable.To this end, the apparatus 600 is designed to (i) identify the properlevel of applanation of the subject blood vessel and associated tissue;(ii) continuously “servo” on this condition to maintain the bloodvessel/tissue properly biased for the best possible tonometricmeasurement; optionally; and (iii) scale the tonometric measurement asneeded to provide an accurate representation of intravascular pressureto the user/operator.

During the simulated annealing process, the controller 611 a controlsthe applanation motor 606 to applanate the artery (and interposedtissue) according to a predetermined profile. Such control schemes mayalso be employed with respect to the lateral and proximal motor driveassemblies if desired, or alternatively a more static approach (i.e.,position to an optimal initial position, and then reposition only uponthe occurrence of an event causing significant misalignment). In thisregard, it will be recognized that the control schemes for theapplanation motor and the lateral/proximal positioning motor(s) may becoupled to any degree desired consistent with the invention.

The apparatus 600 is also configured to apply the methodologies of thefirst, second, third and fourth processes 102, 104, 106 and 108previously discussed with respect to FIGS. 1-5. Details of exemplaryimplementations of these latter methodologies are described elsewhereherein.

The physical apparatus 600 of FIG. 6 comprises, in the illustratedembodiment, a substantially self-contained unit having, inter alia, acombined pressure transducer 622 and applanation device 600, motorcontrollers 611, RISC digital processor 608 with associated synchronousDRAM (SDRAM) memory 617 and instruction set (including scaling lookuptables), display LEDs 619, front panel input device 621, and powersupply 624. In this embodiment, the controllers 611 are used to controlthe operation of the combined pressure transducer/applanation device,with the control and scaling algorithms are implemented on a continuingbasis, based on initial operator/user inputs.

For example, in one embodiment, the user input interface comprises aplurality (e.g., two) buttons disposed on the face of the apparatushousing (not shown) and coupled to the LCD display 679. The processorprogramming and LCD driver are configured to display interactive promptsvia the display 679 to the user upon depression of each of the twobuttons.

Furthermore, a patient monitor (PM) interface circuit 691 shown in FIG.6 may be used to interface the apparatus 600 to an external orthird-party patient monitoring system. Exemplary configurations for suchinterfaces 691 are described in detail in U.S. patent application Ser.No. 10/060,646 entitled “Apparatus and Method for InterfacingTime-Variant Signals” filed on Jan. 30, 2002 and patented as U.S. Pat.No. 7,317,409 on Jan. 8, 2008, and assigned to the Assignee hereof,which is incorporated by reference herein in its entirety, althoughother approaches and circuits may be used. The referenced interfacecircuit has the distinct advantage of automatically interfacing withliterally any type of patient monitor system regardless of itsconfiguration. In this fashion, the apparatus 600 of the presentinvention coupled to the aforementioned interface circuit allowsclinicians and other health care professionals to plug the apparatusinto in situ monitoring equipment already on hand at their facility,thereby obviating the need (and cost) associated with a dedicatedmonitoring system just for blood pressure measurement.

Additionally, an EEPROM 652 is physically coupled to the pressuretransducer 622 as shown in FIG. 6 so as to form a unitary unit which isremovable from the host apparatus 600. The details of the constructionand operation of exemplary embodiments of such coupled assemblies aredescribed in detail in co-owned U.S. Pat. No. 6,676,600, entitled “SmartPhysiologic Parameter Sensor and Method”, issued Jan. 13, 2004, assignedto the Assignee hereof, and incorporated by reference herein in itsentirety, although other configurations clearly may be substituted. Byusing such a coupled and removable arrangement, both the transducer 622and EEPROM 652 may be readily removed and replaced within the system 600by the operator.

It is also noted that the apparatus 600 described herein may beconstructed in a variety of different configurations, and using avariety of different components other than those specifically describedherein. For example, it will be recognized that while many of theforegoing components such as the processor 608, ADC 609, controller 611,and memory are described effectively as discrete integrated circuitcomponents, these components and their functionality may be combinedinto one or more devices of higher integration level (e.g., so-called“system-on-chip” (SoC) devices). The construction and operation of suchdifferent apparatus configurations (given the disclosure providedherein) are readily within the possession of those of ordinary skill inthe medical instrumentation and electronics field, and accordingly notdescribed further herein.

The computer program(s) for implementing the aforementioned first,second, third and fourth processes are also included in the apparatus600. In one exemplary embodiment, the computer program comprises anobject (“machine”) code representation of a C⁺⁺ source code listingimplementing the methodology of FIGS. 1-5, either individually or incombination thereof. While C⁺⁺ language is used for the presentembodiment, it will be appreciated that other programming languages maybe used, including for example VisualBasic™, FORTRAN, and C⁺. The objectcode representation of the source code listing is compiled and may bedisposed on a media storage device of the type well known in thecomputer arts. Such media storage devices can include, withoutlimitation, optical discs, CD ROMs, magnetic floppy disks or “hard”drives, tape drives, or even magnetic bubble memory. These programs mayalso be embedded within the program memory of an embedded device ifdesired. The computer program may further comprise a graphical userinterface (GUI) of the type well known in the programming arts, which isoperatively coupled to the display and input device of the host computeror apparatus on which the program is run.

In terms of general structure, the program is comprised of a series ofsubroutines or algorithms for implementing the applanation and scalingmethodologies described herein based on measured parametric dataprovided to the host apparatus 600. Specifically, the computer programcomprises an assembly language/micro-coded instruction set disposedwithin the embedded storage device, i.e. program memory, of the digitalprocessor or microprocessor associated with the hemodynamic measurementapparatus 600. This latter embodiment provides the advantage ofcompactness in that it obviates the need for a stand-alone PC or similarhardware to implement the program's functionality. Such compactness ishighly desirable in the clinical and home settings, where space (andease of operation) are at a premium.

As previously noted, one of the significant advantages of the presentinvention relates to its flexibility; i.e., that it is essentiallyagnostic to the hardware/firmware/software on which it is used, and canbe readily adapted to various different platforms or systems formeasuring hemodynamic or other physiologic parameters. For example, themethods and apparatus of the present invention are substantiallycompatible with, inter alia, those described in: U.S. patent applicationSer. No. 10/393,660 entitled “Method and Apparatus for Control ofNon-Invasive Parameter Measurements” filed on Mar. 20, 2003 and patentedas U.S. Pat. No. 7,291,112 on Nov. 6, 2007; co-pending U.S. patentapplication Ser. No. 10/269,801 entitled “Apparatus and Methods forNon-Invasively Measuring Hemodynamic Parameters” filed on Oct. 11, 2002and published as U.S. Patent Publication No. 2004/0073123 on Apr. 15,2004; U.S. patent application Ser. No. 10/920,999 entitled “Apparatusand Methods for Non-Invasively Measuring Hemodynamic Parameters” filedon Aug. 18, 2004 and published as U.S. Patent Publication No.2005/0080345 on Apr. 14, 2005; U.S. patent application Ser. No.11/336,222 entitled “Apparatus and Methods for Non-Invasively MeasuringHemodynamic Parameters” filed on Jan. 20, 2006 and published as U.S.Patent Publication No. 2006/0184051 on Aug. 17, 2006; U.S. patentapplication Ser. No. 09/534,900 entitled “Method and Apparatus forAssessing Hemodynamic Parameters within the Circulatory System of aLiving Subject” filed on Mar. 23, 2000 and issued as U.S. Pat. No.6,554,774 on Apr. 29, 2003, each of the foregoing assigned to theAssignee hereof and incorporated by reference herein in its entirety.

It is noted that many variations of the methods described above may beutilized consistent with the present invention. Specifically, certainsteps are optional and may be performed or deleted as desired.Similarly, other steps (such as additional data sampling, processing,filtration, calibration, or mathematical analysis for example) may beadded to the foregoing embodiments. Additionally, the order ofperformance of certain steps may be permuted, or performed in parallel(or series) if desired. Hence, the foregoing embodiments are merelyillustrative of the broader methods of the invention disclosed herein.

While the above detailed description has shown, described, and pointedout novel features of the invention as applied to various embodiments,it will be understood that various omissions, substitutions, and changesin the form and details of the device or process illustrated may be madeby those skilled in the art without departing from the spirit of theinvention. The foregoing description is of the best mode presentlycontemplated of carrying out the invention. This description is in noway meant to be limiting, but rather should be taken as illustrative ofthe general principles of the invention. The scope of the inventionshould be determined with reference to the claims.

What is claimed is:
 1. Transient event-resistant apparatus configured tomaintain an optimal level of compression between one or more sensors anda blood vessel, said transient event-resistant apparatus comprising:said one or more sensors configured to be disposed proximate said bloodvessel; a data storage apparatus; and a digital processor apparatusconfigured to run a computer program thereon, said computer programcomprising a plurality of instructions which are configured to, whenexecuted by said digital processor apparatus, cause said transientevent-resistant apparatus to: analyze a first plurality of signalsgenerated by said one or more sensors at a first location proximate tosaid blood vessel; obtain first data related to one or more firstparameters measured by said one or more sensors at said first location;generate a first plurality of control signals for a motor configured toadjust a position of each of said one or more sensors; store said firstdata at said data storage apparatus; cause placement of said one or moresensors at one or more second locations proximate to said blood vessel;obtain second data related to one or more second parameters measured bysaid one or more sensors at said one or more second locations; andprocess said second data with regards to said first data to determinedata indicative of an optimized location, wherein said process of saidsecond data with respect to said first data at least in part comprises:application of a correction factor to said second data to generatecorrected data; assignment of a value of closeness of said one or moresecond locations to said optimized location based at least in part onsaid corrected data; calculation of a difference between said value ofcloseness at said one or more second locations and an assigned valueassigned of closeness of said first location to said optimized location;and based at least in part on said difference, determination of a sizeof a dither value.
 2. The transient event-resistant apparatus of claim1, wherein said one or more sensors comprises one or more pressuretransducers, said one or more pressure transducers housed in anapplanation assembly, said applanation assembly in signal communicationwith said digital processor apparatus and configured to cause anapplanator to applanate said blood vessel.
 3. The transientevent-resistant apparatus of claim 2, wherein said applanator isconfigured to vary a level of applanation of said blood vessel in orderto maintain said blood vessel in an optimal state of compression forsignal obtainment.
 4. The transient event-resistant apparatus of claim1, wherein said first plurality of control signals comprises at least aninstruction to move said one or more sensors a distance between a targetposition and said first location, said distance derived as a function ofa value associated with a closeness of said first location to an optimalposition based at least in part on said analysis of said first pluralityof signals.
 5. The transient event-resistant apparatus of claim 1,wherein said second data at said one or more second locations isobtained via: placement of said one or more sensors at a first one ofsaid one or more second locations; applanation of said blood vessel atsaid first one of said one or more second locations; and measurement ofa plurality of pulse beats.
 6. A method of operating a transientevent-resistant apparatus, said transient event-resistant apparatus (i)configured to maintain an optimal level of compression between one ormore sensors and a blood vessel, and (ii) comprising at least one ormore sensors, data storage apparatus, and digital processor apparatus,said digital processor apparatus in signal communication with each ofsaid one or more sensors, said data storage apparatus, and a motorizedapparatus configured to control positioning of said one or more sensors,said method comprising: receiving a first plurality of signals from saidone or more sensors disposed at a first location proximate to said bloodvessel; based at least in part on said receipt of said first pluralityof signals, obtaining first data related to one or more first parametersmeasured by said one or more sensors at said first location;algorithmically analyzing said first plurality of signals using at leasta computer program configured to execute on said digital processorapparatus; based at least in part on said algorithmically analyzing,generating a first plurality of control signals for said motorizedapparatus, said first plurality of control signals configured to causeadjusting of a position of each of said one or more sensors; storingsaid first data at said data storage apparatus; causing placement, viasaid motorized apparatus, of said one or more sensors at one or moresecond locations proximate to said blood vessel; obtaining second datarelated to one or more second parameters measured by said one or moresensors at said one or more second locations; and processing said seconddata with regards to said first data to determine data indicative of anoptimized location, wherein said processing of said second data withrespect to said first data at least in part comprises: applying acorrection factor to said second data to generate corrected data;assigning a value of proximity of said one or more second locations tosaid optimized location based at least in part on said corrected data;determining a difference between said value of proximity at said one ormore second locations and an assigned value assigned of proximity ofsaid first location to said optimized location; and based at least inpart on said difference, determining a size of a dither value.
 7. Themethod claim 6, wherein said first plurality of control signalscomprises data relating to at least an instruction to move said one ormore sensors a first distance between a target position and said firstlocation, said distance derived as a function of a value associated witha confidence level related to a proximity of said first location to anoptimal position, the confidence level based at least in part on saidanalysis of said first plurality of signals; and said method furthercomprises causing movement, via said motorized apparatus, of said one ormore sensors said first distance from said first location to said targetposition.
 8. The method of claim 6, wherein said second data at said oneor more second locations is obtained via: causing placement of said oneor more sensors at a first one of said one or more second locations;causing applanation of said blood vessel at said first one of said oneor more second locations; and receiving signals indicative of ameasurement of a plurality of pulse beats from said one or more sensorsdisposed at said first one of said one or more second locations.